Protective effect of edaravone against cyclosporine-induced chronic nephropathy through antioxidant and nitric oxide modulating pathways in rats

Background: Cyclosporine A [CsA] is an immunosuppressant with therapeutic indications in various immunological diseases; however, its use is associated with chronic nephropathy. Oxidative stress has a crucial role in CsA-induced nephrotoxicity. The present study evaluates the protective effect of edaravone on CsA-induced chronic nephropathy and investigates its antioxidant and nitric oxide modulating property

Methods: Male Sprague-Dawley rats [n=66] were distributed into nine groups, including a control [group 1] [n=7]. Eight groups received CsA [15 mg/kg] for 28 days while being treated. The groups were categorized as: - Group 2: Vehicle [n=10]. - Groups 3, 4, and 5: Edaravone [1, 5, and 10 mg/kg] [n=7 each]. - Group 6: Diphenyliodonium chloride, a specific endothelial nitric oxide synthase [eNOS] inhibitor [n=7]. - Group 7: Aminoguanidine, a specific inducible nitric oxide synthase [iNOS] inhibitor [n=7]. - Group 8: Edaravone [10 mg/kg] plus diphenyliodonium chloride [n=7]. - Group 9: Edaravone [10 mg/kg] plus aminoguanidine [n=7]. Blood urea nitrogen and serum creatinine levels, malondialdehyde, superoxide dismutase, and glutathione reductase enzyme activities were measured using standard kits. Renal histopathological evaluations and measurements of eNOS and iNOS gene expressions by RT-PCR were also performed. Data were analyzed using one-way analysis of variance [ANOVA] followed by Tukey's test [SPSS software version 18.0]

Results: Edaravone [10 mg/kg] significantly attenuated CsA-induced oxidative stress, renal dysfunction, and kidney tissue injury. Aminoguanidine improved the renoprotective effect of edaravone. Edaravone reduced the elevated mRNA level of iNOS, but could not alter the level of eNOS mRNA significantly

Conclusion: Edaravone protects against CsA-induced chronic nephropathy using antioxidant property and probably through inhibiting iNOS gene expression

Preparation of a selective l-phenylalanine imprinted polymer implicated in patients with phenylketonuria

Molecular imprinting is a method for synthesizing polymers with structure-selective adsorption properties with applications such as, selectivity binding, drug delivery systems and anti-bodies. The present study aims at optimizing the preparation of molecularly imprinted polymer [MIP] against 1-phenylalanine, in order to increase phenylalanine-binding in Enzymatic Intestinal Simulated Fluid [ESIF]. The MIP for 1-phenylalanine, as a water-soluble template, was successfully synthesized without derivatization. Synthesization was done by a UV polymerization method in which methacrylic acid [MAA], as a functional monomer, and ethylene glycol dimethacrylate [EGDMA], as a cross-linker, were used in the presence of five different porogenic solvents including; acetonitrile, tetrahydrofuran [THF], chloroform, toluene and dimethyl sulfoxide [DMSO]. The selectivity of the MIP was examined using 19 different amino acids in human serum and was evaluated by HPLC. In addition, morphological studies were conducted using SEM. The results showed that the obtained MIP with acetonitrile had the highest capacity and selectivity compared with other solvents. The data indicated that Phe-binding to MYS was significantly more than the former binding to NIP in EIS1 [p<0.05]. Moreover, in comparison wthNIP and control grouf MIP showed abetter selectivity and binding for Phe. This could be used for the reduction of Phe in human serum samples of Phenylketonuria. Our findings suggest that the MIP against PI prepared with acetonitrile, showed a good selectivity ai binding, which caused a reduction of blood Phe concentrati in enzymatic simulated intestinal fluid and human serum sam] of Phenylketonuria

Stereological study of the effect of ginger's alcoholic extract on the testis in busulphan-induced infertility in rats

In traditional medicine zingiber officinale used to regulate female menstural cycle and treat male infertility. Recent studies have suggested the possible role of ginger extract in improving the testicular damage of busulfan. The aim of this study was to evaluate the effects of zingiber officinale on the sperm parameters, testosterone level and the volume of the testes and seminiferous tubules by stereological methods. Fifty rats were divided into four groups. All the rats were given a single intraperitoneally injection of 5mg/kg busulfan solution. The first group was kept as busulfan control, while the other groups were orally administrated ginger extract in graded doses of 50, 100 and 150mg/kg b.wt, for 48 consecutive days. At the end, all animals were anesthetized and their testes and vas deference were removed, fixed, embedded, and stained. The volume of testes and seminiferous tubules were estimated by cavalieri methods. The result showed, that zingiber officinale increased the volumes of seminiferous tubule in 100mg/kg treated group compared to control group. Sperm count [706x10[5] and 682x10[5]] and the level of testosterone [50.90 ng/mL and 54.10 ng/mL] enhanced in 100 mg/kg and 150 mg/kg treated groups compared to control group [p=0.00]. It seems that zingiber officinale stimulate male reproductive system in induce busulfan infertility

study of apomorphine effects and heterogeneity in the medial prefrontal cortex on the dopaminergic behaviors of rats

While the nucleus accumbens and the striatum have received much attention regarding their roles in stereotyped behaviors, the role of the medial prefrontal cortex [mPFC] has not been investigated to the same degree. Few studies have reported the role of the mPFC in dopaminergic induction of locomotor hyperactivity. The mPFC is a heterogeneous area [the anterior cingulated, prelimbic, and the infralimbic] with particular inputs and outputs to subcortical regions that may have different effects on stereotyped behaviors. In this work, apomorphine, a non-specific dopamine agonist, was microinjected into the three different subregions of the mPFC for induction of stereotyped behaviors to show the role of the three subareas of the mPFC on behaviors and its heterogeneity. Cannulas implanted in the infralimbic, the prelimbic or the anterior cingulated areas of the mPFC. Apomorphine microinjected at five doses and then behaviors recorded. There were significant differences among three areas. The rats receiving apomorphine in the anterior cingulated showed less sniffing and climbing but more chewing behaviors. Yawning observed more significantly in the rats given apomorphine in the prelimbic area. The rats getting apomorphine in the infralimbic of the mPFC showed more climbing behavior. It was indicated that manipulation of the dopaminergic system in mPFC alters behaviors and with regard to this, there may be heterogeneity among its three subregions